Stress study offers clues for new antidepressant drugs

LONDON - Scientists have worked out the way in which stress hormones reduce the number of new brain cells - a process linked to depression - and say their work should help researchers develop more effective antidepressants.

The scientists identified a protein largely responsible for the long-term detrimental effect of stress on cells.

They also successfully used an experimental drug compound to block this effect, pointing to a possible way of developing new antidepressants, the study published in the Proceedings of the National Academy of Sciences said.

Major depression affects about 20 percent of people at some time in their lives. The World Health Organization (WHO) predicts that by 2020, depression will rival heart disease as the health disorder with the highest global disease burden.

Treatment for depression involves either medication or counseling - and often a combination of both.

But while there are many antidepressants on the market, including top sellers such as Prozac and Seroxat, it is widely accepted that many antidepressants work in only half of patients half of the time, and drugmakers are struggling to come up with a new generation of drugs.

Depression is linked to changes in a process called neurogenesis - the ability of the adult brain to continue producing new brain cells.

At a molecular level, stress is known to increase levels of a hormone called cortisol, which in turn acts on a receptor called the glucocorticoid receptor. But the exact mechanism behind this process has been unclear.

A team under Carmine Pariante of King's College London's Institute of Psychiatry, who led the research, studied human hippocampal stem cells - source of new cells in the human brain.

They gave the cells cortisol to measure the effect on neurogenesis and found that a protein called SGK1 was important in mediating the effects.

By measuring the effect of cortisol over time, they found that increased levels of SGK1 prolong the damaging impact of stress hormones on neurogenesis.

Next, the researchers used an experimental drug compound known to inhibit SGK1 and found it blocked the negative effects of stress hormones, leading to an increase in new brain cells.

The team confirmed the results by studying levels of SGK1 in animals and then in blood samples from people with depression.